Patients treated with olaparib had a median progression-free survival of 8.4 months compared with 4.8 months among patients randomized to placebo, Jonathan Ledermann, MD, said during a press briefing prior to the American Society of Clinical Oncology meeting.

Adverse events were more common with olaparib, especially nausea, but overall tolerability was good, said Ledermann, of University College London.

"This is the first study to demonstrate a statistically significant benefit of maintenance treatment for platinum-sensitive, relapsed serous ovarian cancer," he said. "At the time of the analysis, 50% of olaparib patients and 16% of placebo patients were still on treatment."

A majority of patients with BRCA-related ovarian cancer have homologous recombination deficiency, a defect that allows cancer cells to repair DNA damage, including chemotherapy-induced damage. About 15% of patients with ovarian cancer have tumors with inherited BRCA mutations.

Additionally, about half of ovarian cancers have homologous recombination deficiency resulting from noninherited BRCA mutations and from BRCA-independent defects, said Ledermann. Most often, these tumors are high-grade serous cancers, the most common ovarian cancer subtype.

Tumors that also have retained platinum sensitivity appear to be especially susceptible to PARP inhibition.

The PARP inhibitor olaparib has demonstrated activity against high-grade serous ovarian cancer, irrespective of BRCA mutation status. The promising early results led to the phase II, randomized, placebo-controlled trial reported by Ledermann.

The study involved 265 patients who had received at least two prior platinum-based regimens and remained in partial or complete response to the most recent regimen. The trial design reflected the unmet need for an effective maintenance therapy to delay recurrence after therapy for relapsed disease, said Ledermann.

Investigators in 16 countries randomized the patients to olaparib or placebo, and treatment continued until recurrence or development of unacceptable toxicity.

The primary endpoint was progression-free survival.

When the trial ended, 153 patients had progressed. The difference in progression-free survival favoring treatment with olaparib translated into a 65% reduction in the hazard ratio (HR 0.35, P<0.00001).

Analysis of time to progression, as assessed by levels of the CA-125 cancer biomarker or by RECIST clinical criteria, also showed a significant 65% reduction in the hazard ratio in favor of olaparib (P<0.00001).

Median time to progression was 8.3 months in the olaparib arm and 3.7 months in the placebo arm.

The most common adverse events (all grades) in the olaparib arm were nausea (68% versus 35% in the placebo arm), fatigue (49% versus 38%), and vomiting (32% versus 14%).

The study is noteworthy for two reasons, said Mark G. Kris, MD, an ASCO spokesperson. The results suggest that olaparib has the potential to fulfill the previously unmet need for a maintenance therapy to prolong the time the disease is controlled after completion of successful chemotherapy.

Second, the results provide another demonstration of the potential of targeted therapy in oncology: Scientists identified a specific defect in the cancer cells and developed a specific therapy that exploited the defect to prolong patients' lives.

"That is our dream of personalized care, and this is one example of that dream approaching reality," said Kris, of Memorial Sloan Kettering Cancer Center in New York.

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